Preliminary Results Find Inactivated SARS-CoV-2 Virus-Based COVID-19 Candidate Vaccine Safe

A Chinese COVID-19 vaccine candidate based on the inactivated whole SARS-CoV-2 virus (BBIBP-CorV) is safe and elicits an antibody response, findings from a small early-phase randomized clinical trial published today in Infectious Diseases from The Lancet diary have found.

A previous clinical trial reported similar results for a different vaccine that is also based on the inactivated whole SARS-CoV-2 virus, but in that study the vaccine was only tested in people younger than 60 years.

The latest study included participants between the ages of 18 and 80 and found that antibody responses were induced in all recipients. Participants aged 60 and over responded more slowly, taking 42 days before antibodies were detected in all recipients compared to 28 days for participants aged 18 to 59. Antibody levels were also lower in people aged 60 to 80 years compared to those aged 18 to 59 (the mean neutralizing antibody titer 42 days after receiving an 8 μg dose of vaccine was 228.7 for those aged 18 to 59). people between 18 and 59 years old and 170.9 for those between 60 and 80 years old).

The trial was not designed to evaluate the efficacy of the vaccine, so it is not possible to say whether the antibody responses induced by the vaccine, called BBIBP-CorV, are sufficient to protect against SARS-CoV-2 infection.

Professor Xiaoming Yang, one of the authors of the study, from the Institute of Biological Products of Beijing Company Limited, Beijing, China, said: “Protection of the elderly is a key goal of a successful COVID-19 vaccine, as this age group is at higher risk of severe illness due to disease. However, vaccines are sometimes less effective in this group because the immune system weakens with age. Therefore, it is encouraging to see that BBIBP-CorV induces responses of antibodies in people 60 years and older, and we believe this warrants further investigation. “

There are currently 42 vaccines for COVID-19 in clinical trials. These vary in type and include DNA plasmid vaccines, inactivated virus vaccines, adenovirus vector vaccines, RNA vaccines, protein subunit vaccines, and virus-like particulate vaccines. Some of these have already been shown to be safe and elicit immune responses in early-phase clinical trials.

The BBIBP-CorV vaccine used in the study reported here is based on a sample of the virus that was isolated from a patient in China. Stocks of the virus were grown in the laboratory using cell lines and then inactivated with a chemical called beta-propionolactone. BBIBP-CorV includes the killed virus mixed with another component, aluminum hydroxide, which is called an adjuvant because it is known to stimulate immune responses.

The first phase of the study was designed to find the optimal safe dose for BBIBP-CorV. It included 96 healthy volunteers between 18 and 59 years old and a second group of 96 participants between 60 and 80 years old. Within each group, the vaccine was tested at three different dose levels (2 µg, 4 µg, and 8 µg, 24 participants per group), with two vaccines administered on days 0 and 28. A fourth group within each age group (24 participants in each age group) received two doses of a placebo vaccine. In total, in phase 1 of the study, 144 participants received the vaccine and 48 received the placebo.

The second phase of the study was designed to identify the optimal schedule for vaccination. 448 participants aged 18 to 59 years were randomly assigned to receive one injection of 8 μg of vaccine or placebo, or two injections of 4 μg of vaccine or placebo (on days 0 and 14, days 0 and 21, or days 0 and 28). In this second phase, there were 112 participants per group, 336 received the vaccine and 112 received the placebo.

Participants were asked to report any adverse events during the first seven days after each vaccination, and the research team verified them. Thereafter, participants recorded any adverse events using paper cards for the next 4 weeks. During phase 1, laboratory tests were carried out after the first and second vaccinations to assess kidney function, liver function, and other organ functions. Blood samples were taken to test for SARS-CoV-2 antibody levels before and after vaccination.

No serious adverse events were reported within 28 days of final vaccination. The most common side effect was pain at the injection site (Phase 1 results: 24% [34/144] of vaccine recipients, versus 6% [3/48] of placebo recipients). A small number of participants reported experiencing a fever (Phase 1 results: 4% [5/144] of vaccine recipients, versus 6% [3/48] of placebo recipients). There were no cases of clinically significant changes in organ function detected in laboratory tests in either group.

The highest antibody responses were obtained with two 4 μg doses of the vaccine on days 0 and 21 or 0 and 28 (the mean neutralizing antibody titers 28 days after the second vaccination were 282.7 for two 4 μg injections on days 0 and 21, and 218.0 for two injections of 4 μg injections on days 0 and 28).

Professor Xiaoming Yang said: “Our findings indicate that a booster injection is necessary to achieve the highest antibody responses against SARS-CoV-2 and could be important for protection. This provides useful information for a phase 3 trial.” .

The authors noted some limitations with the study, including the short duration of follow-up of just 42 days. They also noted that the study did not include children and adolescents under 18 years of age. Trials with these groups will be conducted when full analysis of the data from the adult groups is completed, the researchers say.

In a linked comment article, Professor Larisa Rudenko, who was not involved in the study, from the Institute of Experimental Medicine in St. Petersburg, Russia, said: “[…] Further studies are needed to establish whether inactivated SARS-CoV-2 vaccines are capable of inducing and maintaining virus-specific T cell responses, because the help of CD4 positive T cells is important for optimal antibody responses, as well as for cytotoxic CD8. -activation of positive T cells, which, in turn, are crucial for viral elimination if protection mediated by neutralizing antibodies is incomplete “.